Night sleep EEG and daytime sleep propensity in adult hypopituitary patients with growth hormone deficiency before and after six months of growth hormone replacement

Abstract

Background: Hypopituitary patients with growth hormone deficiency (GHD) complain of reduced vitality, general fatigue, lack of concentration, irritability and reduced alertness during daytime. It is unclear whether these symptoms are primarily due to GH-deficiency and/or secondary to GHD related sleep impairments. Bi-directional interactions between the somatotropic system and human sleep patterns are well established. However, data on the effect of GH either in subjects without GHD or in patients with GHD under GH replacement therapy on the sleep electroencephalogram (EEG) are controversial. No reports exist about objective measures of daytime sleepiness in GH deficient patients before and during GH-therapy.

Objective: To assess the effects of GH on nocturnal and daytime sleep in adult patients with GHD before and during recombinant human GH (rhGH, Somatropin) replacement therapy.

Methods: Eighteen adult patients with GHD (4 women and 14 men) participated in the study. Mean age at the beginning of the study was 48.5 years (range 27-64 years). Ten patients were recruited from a double-blind, randomized placebo controlled trial over 6 months, followed by an open treatment period of 6 additional months (Group I). In all patients from this group, only the effects of the first 6 months of GH treatment were assessed. Eight additional patients were treated in an open study design for 6 months (Group II). Nocturnal sleep recordings and daytime sleep EEGs with a multiple sleep latency test were performed at baseline and after 6 months of additional GH replacement therapy.

Results: One patient dropped out due to side effects and was not included in sleep analysis. IGF-1 levels were increased in all patients, partially in a supraphysiologic range. Side effects were mainly mild but in one patient (from group II), general muscle pain led to interruption of the study. Therefore sleep analysis was only done in 17 patients. Sleep parameters were comparable to healthy control groups from the literature. GH substitution over 6 months did neither affect total sleep time nor times spent in different sleep stages. REM sleep density was also not changed. Daytime sleep propensity as measured by the multiple sleep latency test was not influenced by GH treatment.

Conclusions: GH replacement does neither affect night sleep nor daytime sleep propensity in GH deficient hypopituitary adults. GH substitution has no sleep disturbing effect.